The global cerebral spinal fluid (CSF) management market is anticipated to reach $1.4B by 2022. Problems related to CSF leaks and intracranial infections, such as meningitis, can be caused by trauma, neurosurgical procedures, and pre-existing defects in various regions of the skull. These problems are a major cause of neurosurgical morbidity and have limited treatment options. The median cost of fixing a CSF leak was over $29,000. Currently available commercial dural sealants include fibrin glues and biopolymers, such as BioGlue and DuraSeal, respectively. These products are limited by their poor performance in aqueous environments, weak adhesion on wet tissues, short degradation time, dangerously high swelling ratios, and cytotoxicity. Clinical outcomes are often unsatisfactory and post-operative CSF leakage risk remains high, often incurring significant additional health care costs. The primary goal of the Phase I proposal is to develop Aleo BME's proprietary biphasic glue (BP Glue) for the repair of compromised dura in the brain. Leveraging the natural plant adhesion mechanisms utilized by English ivy to adhere to diverse substrates and particle packing theory in developing mechanically strong composite materials in cement industry, BP Glue is nature-inspired, fast- curing biomaterial capable of forming strong adhesive sealing in an aqueous environment, bacterial impermeable, degradable, and may be easily applied in a medical setting. BP Glue mitigates serious risks associated with post-surgical leaks, infections, and its predictable degradation process accelerates healthy tissue repair and integration, allowing surgeons to successfully treat patients that would otherwise endure lengthy recoveries fraught with serious complications. The novelty of BP Glue lies in the unique combination of plant-inspired bioadhesion strategy and particle packing theory borrowed from cement industry for biomimetic wet tissue adhesives development. The BP Glue system is composed of two WPU components with opposite charges (+)/(-) (Fig. 1). The scientific premise of the proposal is as follows 1) BP Glue demonstrates a 6 fold greater wet tissue lap shear strength, 3 fold greater burst strength and 11 folder greater T-pull strength than the commercial gold standards, fibrin glue and DuraSeal, 2) BP Glue is effective to prevent CSF leakage in a preclinical animal model, and 3) BP Glue adhesion mechanism simulates that of English-Ivy in which nanoparticles secreted by English-Ivy are ionically crosslinked to form an inter-locking film capable of binding to rough surfaces, such as buildings, trees or biological tissues in combination with that of particle packing theory under which compositing particles with optimal size difference maximizes the cohesive strength of the resultant composite materials. The expected outcome of this proposal is that we will develop a new type of fully synthetic bioinspired biodegradable adhesive sealant and validate the feasibility for CSF leak prevention and dura repair in a rat CSF leak model and lay a foundation for large animal studies in Phase II.